The GRAS Oversight and Transparency Act directs the Secretary of Health and Human Services, through the Commissioner of Food and Drugs, to establish a GRAS Review Board. This Board's primary purpose is to review the validity of "covered GRAS designations," which are manufacturer-made designations prior to 2000 asserting that a food substance is generally recognized as safe for its intended use. The Board will comprise voting members from various federal agencies, including HHS, USDA, FDA, and EPA, along with non-voting members from academia and the food manufacturing industry, all serving five-year terms without compensation.

The Board's duties include identifying the scope of covered GRAS designations by soliciting information from food manufacturers, categorizing these designations into Tier 1, 2, or 3 for review priority, and then conducting reviews to determine their validity. Manufacturers are mandated to provide notice of their covered GRAS designations within 90 days of the Act's enactment, and failure to comply can result in civil penalties or the substance being treated as an unapproved food additive. If the Board determines a substance is not shown to be safe, it will notify the Secretary and Congress, recommending revocation of the GRAS designation.

Upon receiving a revocation recommendation, the Secretary may revoke a designation, providing the manufacturer 180 days to submit scientific evidence of safety before a final decision. The Secretary must also establish procedures to ensure manufacturer compliance with revocations, including ceasing distribution and recalling products. The Board is required to submit public reports on its reviews and recommendations to the Secretary and Congress, with deadlines ranging from two to ten years depending on the review tier. The Board and the Act itself will terminate ten years after enactment.